Helicobacter pylori (Hp) infection almost invariably results in chronic antral gastritis, but only a proportion of patients develop peptic ulcer. Some Hp strains may be more ulcerogenic than others, but some ulcerogenic mechanisms may also depend on the type of the host immune response. In this study, the antigen specificity and the cytokine profile of 53 Hp-specific CD4+ T cell clones derived from the antral mucosa of five patients with Hp-induced uncomplicated chronic gastritis (CG) were assessed and compared with those of 34 Hp-specific CD4+ T cell clones derived from six Hp-infected patients with chronic gastritis and peptic ulcer (CG-PU). The majority (28/34; 82%) of gastric Hp-specific T cell clones from CG-PU patients expressed the Th1 profile and 17 (all Th1) of the 34 clones were specific for cytotoxin-associated protein (CagA). In contrast, 34 (64%) of the 53 Hp-specific gastric T cell clones derived from CG patients were able to secrete both Th1 and Th2 cytokines (Th0 profile) and only 36% expressed a polarized Th1 profile. The majority (85%) of Hp-specific clones from CG patients recognized Hp antigens other than CagA, since 13/53 (25%) were specific for urease, 6 (11%) for VacA, 6 (11%) for HSP and 20 (38%) for other undefined Hp antigens. Results provide evidence that the type of T helper cell response against Hp may vary according to the antigen involved and suggest that a polarized Th1 response may play a role in the genesis of peptic ulcer, whereas a local Th0 response, including interleukin-4 production, may represent an individual host factor which contributes to lower the degree of gastric inflammation and prevent ulcer complication.

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Abstract:CD3O is a member of the tumor necrosis factor

T-cells and their cytokines are thought to play a major role in the genesis of cellular infiltration and rejection in human kidney allografts. Production of Th1 (IFN-gamma) and Th2-type (IL-4 and IL-5) cytokines was assessed in a large series of T-cell clones, derived from core biopsies of kidney grafts in 10 patients with acute interstitial grade I/II rejection (AIR), 6 patients with a histology of "borderline rejection" (BLR) and 3 with cyclosporine A (CsA) toxicity, all receiving standard maintenance immunosuppression. Biopsies were pre-cultured in IL-2 in order to preferentially expand T-cells activated in vivo, and T-cell blasts were cloned with phytohemagglutinin (PHA) and IL-2 using a highly efficient (23 to 98%) cloning technique. A total of 483 T-cell clones obtained from AIR episodes were compared with 346 and 132 clones derived from patients with BLR episodes and CsA toxicity, respectively. In two series of 22 AIR and 77 BLR T-cell clones, alloreactivity against donor cells was shown by 25 and 14% of CD8+ and 21 and 4% of CD4+ clones, respectively. When stimulated by donor-derived EBV B-cells, all these alloreactive clones produced IFN-gamma, but not IL-4 or IL-5 (Th1 clones). Upon stimulation with PHA, the principal qualitative and quantitative differences between AIR- and BLR-derived T-cell clones were that cells derived from AIR patients: (i) showed significantly higher proportions (80 +/- 15 vs. 55 +/- 13%) of Th1 clones in their progeny; (ii) included smaller proportions (3 +/- 4 vs. 20 +/- 17%) of clones incapable of producing IFN-gamma, IL-4 or IL-5 ('null' clones); and (iii) produced significantly higher quantities of IFN-gamma (100 +/- 50 vs. 36 +/- 7 U/10(6) cells/ml), these quantities also being significantly correlated (r = 0.83) with the degree of interstitial graft infiltration (item 'i' in the Banff histological grading). The clones derived from CsA toxicity biopsies exhibited a pattern very similar to that found in BIR cases. These data lead us to conclude that the powerful inflammatory response elicited in acute rejection of a kidney graft recruits and activates both allospecific and non-specific Th1 effector cells, which are primed to high IFN-gamma production. Our results also suggest that IFN-gamma could contribute, at least in part, to the degree of graft infiltration and to the severity of the rejection episode.